Distinct contribution of white matter damage to the clinical syndrome of Alzheimer's disease

Alzheimer's disease is a neurodegenerative disorder affecting over 5.1 million individuals in the United States today. The dementia exhibited with the disease is currently thought to be primarily due to amyloid plaques and neurofibrillary tangles. However, several other changes occur, including severe white matter damage that is yet to be fully understood. Such white matter damage includes white matter lesions (WML), which are more common in individuals with Alzheimer's disease than in non-demented individuals. WML are of presumed vascular origin because they show features of small-vessel disease and are more prevalent in individuals with vascular risk. It is currently unclear whether WML are linked to the neurodegenerative pathologies of Alzheimer's disease or are an independent factor that influences clinical course. In this work, we used sensitive diffusion MRI measures to determine that the tissue properties of WML slightly differed microstructurally between individuals with Alzheimer's disease and non-demented controls, and were strongly related to ventricular enlargement. In order to further understand the role of WML, we factored the volume of WML with four other neuroimaging markers affected in Alzheimer's disease and discovered two statistically distinct factors presumed to be due to differing underlying disease processes. One process strongly related to volume and tissue properties of WML, ventricular enlargement, age and cerebral perfusion, while the other process related to imaging markers associated with neurodegeneration. A decrease over time in the first process, interpreted as the age- and vascular-related factor, led to similar cognitive decline as the neurodegenerative factor independently, demonstrating the potential added therapeutic benefit of targeting this disease process that is distinct from the classical neurodegenerative component of the disease.

Department dc:contributor.department

Harvard--MIT Program in Health Sciences and Technology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2016

Author dc:creator

• Coutu, Jean-Philippe

Advisor dc:contributor.advisor

• David H. Salat.

• Harvard--MIT Program in Health Sciences and Technology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/103503

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/103503